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February 13, 2009

Researchers Compile Common Cold Family Tree

by Sam Savage

A new study has shed light on the secrets of the common cold, researchers reported on Thursday.

Scientists at the University of Maryland School of Medicine, the University of Wisconsin-Madison and the J. Craig Venter Institute collaborated to sequence and analyze the cold virus. As a result, they were able to configure a family tree of the common cold.

"We've had bits and pieces of these things for a long time," said Ann Palmenberg, of UW-Madison's Institute for Molecular Virology and the lead author of the new study published in the journal Science.

"Now, we have the full genome sequences and we can put them into evolutionary perspective."

Researchers noted that human rhinoviruses are organized into about 15 small groups that come from distant ancestors, which they say explains why the "no one drug fits all" approach has been successful.

"We know a lot about the common cold virus," Palmenberg said, "but we didn't know how their genomes encoded all that information. Now we do, and all kinds of new things are falling out."

Humans are constantly exposed to cold viruses, and each year adults may endure two to four infections, while schoolchildren can catch as many as 10 colds, researchers said.

"There has been no success in developing effective drugs to cure the common cold, which we believe is due to incomplete information about the genetic composition of all these strains," said Stephen B. Liggett, professor of medicine and physiology at the University of Maryland School of Medicine and director of its Cardiopulmonary Genomics Program.

"We generally think of colds as a nuisance, but they can be debilitating in the very young and in older individuals, and can trigger asthma attacks at any age. Also, recent studies indicate that early rhinovirus infection in children can program their immune system to develop asthma by adolescence," he said.

Liggett said their discovery could lead to the development of a handful of specially designed drugs.

"Perhaps several anti-viral drugs could be developed, targeted to specific genetic regions of certain groups. The choice of which drug to prescribe would be based on the genetic characteristics of a patient's rhinovirus infection."

Palmenberg said the wide variety of mutations is the primary reason there will never be a vaccine for the common cold.

"No vaccine, but maybe a drug," she said.

The researchers also found that the human rhinovirus skips a step when it makes its protein product, a shortcut that probably speeds up its ability to make a person feel sick soon after infection.

"This is a new insight," says co-investigator Claire M. Fraser-Liggett, Ph.D., director of the Institute for Genome Sciences and professor of medicine and microbiology at the University of Maryland School of Medicine.

"We would not have had any sort of intuition about this had it not been revealed through genome analysis. Information that comes from this discovery might present a completely different approach in terms of therapy."

They noted as many as 800 mutations in virus samples taken from patients with colds.

"Mutations were found in every area of the genome," said Dr. Liggett.

"It was clear to us that the spectrum of rhinoviruses out there was probably much greater than we realized. Further, we needed to develop a framework from which we could begin to figure out ways to combat these viruses and use their genetic signatures to predict how a specific virus would affect a patient," said Dr. Fraser-Liggett.

Human rhinovirus infection is responsible for half of all asthma attacks and is a factor in bronchitis, sinusitis, middle ear infections and pneumonia. The virus accounts to a major health care burden in the United States including visits to health care providers, cost of over-the-counter drugs for symptom relief, often-inappropriate antibiotic prescriptions and missed work days"”with direct and indirect costs of about $60 billion annually, researchers said.

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Image 2: A multi-institutional team of researchers has deciphered the complete genetic sequences of all of the world's 99 known strains of human rhinovirus, the viruses responsible for the common cold. The sequences provide a detailed blueprint for the virus, showing how new strains develop and revealing pressure points that may lead to new antiviral drugs. Here, a rhinovirus particle at atomic resolution is superimposed over a representation of the RNA molecule that encodes the virus genome. Image courtesy Ann Palmenberg, Jean-Yves Sgro and H. Adam Steinberg

Image 3: This image shows the structure of the human rhinovirus capsid. Courtesy of Dr. Jean-Yves Sgro, University of Wisconsin-Madison